Comparison of two pancreatic enzyme products for exocrine insufficiency in patients with cystic fibrosis

Background: Zenpep (APT-1008) is a pancreatic enzyme product for the treatment of exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF). Methods: Zenpep and Kreon, both containing 25,000 lipase units, were compared in a randomised, double-blind, crossover, non-inferiority study for CF-associated EPI in patients aged ≥12 years. Patients on a standardised diet and stabilised treatment were randomised to two treatment sequences: Zenpep/Kreon or Kreon/Zenpep. The primary efficacy endpoint was the coefficient of fat absorption over 72 h (CFA-72 h). Results: 96 patients (mean age 19.2 years, 60.4% males) were randomised with 83 completers of both sequences comprising the efficacy population. Zenpep demonstrated non-inferiority and equivalence to Kreon in fat absorption (LS mean CFA-72 h: Zenpep, 84.1% [SE 1.1] vs. Kreon, 85.3% [SE 1.1]; p = 0.297). Safety and tolerability were similar. Conclusions: Zenpep is comparable with Kreon in efficacy and safety for the treatment of adolescents and adults with CF-associated EPI. NCT0164139

Effect of Citalopram on Emotion Processing in Humans:A Combined 5-HT [C]CUMI-101 PET and Functional MRI Study

A subset of patients started on a selective serotonin reuptake inhibitor (SSRI) initially experience increased anxiety, which can lead to early discontinuation before therapeutic effects are manifest. The neural basis of this early SSRI effect is not known. Presynaptic dorsal raphe neuron (DRN) 5-HT1A receptors are known to play a critical role in affect processing. Thus we investigated the effect of acute citalopram on emotional processing and the relationship between DRN 5-HT1A receptor availability and amygdala reactivity. Thirteen (mean age 48±9 years) healthy male subjects received either a saline or citalopram infusion intravenously (10 mg over 30 min) on separate occasions in a single-blind, random order, cross-over design. On each occasion, participants underwent a block design face-emotion processing task during fMRI known to activate the amygdala. Ten subjects also completed a positron emission tomography (PET) scan to quantify DRN 5-HT1A availability using [(11)C]CUMI-101.Citalopram infusion when compared to saline resulted in a significantly increased bilateral amygdala responses to fearful vs. neutral faces (Left p=0.025; Right p=0.038 FWE-corrected). DRN [(11)C]CUMI-101availability significantly positively correlated with the effect of citalopram on the left amygdala response to fearful faces (Z=2.51, p=0.027) and right amygdala response to happy faces (Z=2.33, p=0.032). Our findings indicate that the initial effect of SSRI treatment is to alter processing of aversive stimuli, and that this is linked to DRN 5-HT1A receptors in line with evidence that 5-HT1A receptors have a role in mediating emotional processing

Categorical improvements in disease severity in patients with major depressive disorder treated with vilazodone: post hoc analysis of four randomized, placebo-controlled trials

Suresh Durgam,1 Changzheng Chen,1 Carl P Gommoll,1 John Edwards,1 Leslie Citrome2 1Allergan, Jersey City, NJ, USA; 2Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY, USA Background: In three 8-week studies of vilazodone 40 mg/d (NCT00285376, NCT00683592, and NCT01473394) and a 10-week study of vilazodone 20 or 40 mg/d (NCT01473381), adults with major depressive disorder (MDD) showed significantly greater improvement with vilazodone versus placebo in global disease severity as measured by mean change from baseline in Clinical Global Impression of Severity (CGI-S) score. To assess the proportion of patients achieving clinically meaningful improvement, a post hoc pooled analysis was conducted using categorical shifts in disease severity based on CGI-S scores at baseline and end of treatment (EOT). Methods: Analyses were conducted in the pooled intent-to-treat population (N=2,218). Definitions of categorical shifts included CGI-S ≥4 (moderately ill or worse) at baseline to CGI-S ≤2 (normal or borderline ill) at EOT; CGI-S ≥5 (markedly ill or worse) at baseline to CGI-S ≤2 at EOT; and CGI-S ≥6 (severely ill or worse) at baseline to CGI-S ≤3 (mildly ill or better) at EOT. Results: At baseline, 2,217 patients were moderately ill or worse. The percentage who improved to normal or borderline ill was significantly higher with vilazodone than with placebo (40.0% versus 27.8%; odds ratio [OR] =1.7, P<0.001; number needed to treat [NNT] =9). In the 979 patients who were markedly ill or worse at baseline, the percentage who improved to normal or borderline ill was significantly higher with vilazodone than with placebo (36.8% versus 25.5%; OR =1.7, P<0.001; NNT =9). The small number of severely ill patients at baseline (n =43) provided inadequate power to detect statistically significant between-group differences, but an NNT =5 was found for improvement to mildly ill or better. Conclusion: Categorical shift analyses, defined using baseline and EOT CGI-S scores, showed that significantly higher proportions of patients had clinically meaningful improvements in global disease severity with vilazodone 20–40 mg/d versus placebo. This type of analysis may be useful for evaluating the effects of antidepressant treatment in adults with MDD. Keywords: depression, antidepressant, global improvement, clinical tria

Characterizing sexual function in patients with generalized anxiety disorder: a pooled analysis of three vilazodone studies

Anita H Clayton,1 Suresh Durgam,2 Xiongwen Tang,2 Changzheng Chen,2 Adam Ruth,3 Carl Gommoll2 1Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, 2Forest Research Institute, Jersey City, NJ, 3Prescott Medical Communications Group, Chicago, IL, USA Background: Vilazodone has been shown to reduce core symptoms of generalized anxiety disorder (GAD) in three randomized, double-blind, placebo-controlled trials. Since sexual dysfunction (SD) is not well characterized in GAD, a post hoc analysis of these trials was conducted to evaluate the effects of vilazodone on sexual functioning in GAD patients. Materials and methods: Data were pooled from one fixed-dose trial of vilazodone 20 and 40 mg/day (NCT01629966) and two flexible-dose studies of vilazodone 20–40 mg/day (NCT01766401, NCT01844115) in adults with GAD. Sexual functioning was assessed using the Changes in Sexual Functioning Questionnaire (CSFQ). Outcomes included mean change from baseline to end of treatment (EOT) in CSFQ total score and percentage of patients shifting from SD at baseline (CSFQ total score ≤47 for males, ≤41 for females) to normal functioning at EOT. Treatment-emergent adverse events related to sexual functioning were also analyzed. Results: A total of 1,373 patients were included in the analyses. SD at baseline was more common in females (placebo, 46.4%; vilazodone, 49%) than in males (placebo, 35.1%; vilazodone, 40.9%). CSFQ total score improvement was found in both females (placebo, +1.2; vilazodone, +1.6) and males (placebo, +2.1; vilazodone, +1.0), with no statistically significant differences between treatment groups. The percentage of patients who shifted from SD at baseline to normal sexual functioning at EOT was higher in males (placebo, 40.6%; vilazodone, 35.7%) than in females (placebo, 24.9%; vilazodone, 34.9%); no statistical testing was performed. Except for erectile dysfunction and delayed ejaculation in vilazodone-treated males (2.4% and 2.1%, respectively), no treatment-emergent adverse events related to sexual functioning occurred in ≥2% of patients in either treatment group. Conclusion: Approximately 35%–50% of patients in the vilazodone GAD studies had SD at baseline. Vilazodone and placebo had similar effects on CSFQ outcomes in both females and males, indicating a limited adverse impact on sexual functioning with vilazodone. Keywords: vilazodone, generalized anxiety disorder, sexual dysfunction, clinical trials, post hoc analysi